Revising the National Ambient Air Quality Standards: The integration of science and policy

Under the Clean Air Act, Congress granted discretionary decision making authority to the Administrator of the Environmental Protection Agency (EPA). This discretionary authority involves setting standards to protect the public's health with an "adequate margin of safety" based on current scientific knowledge. The Administrator of the EPA is usually not a scientist, and for the National Ambient Air Quality Standard (NAAQS) for particulate matter (PM), the Administrator faced the task of revising a standard when several scientific factors were ambiguous. These factors included: (1) no identifiable threshold below which health effects are not manifested, (2) no biological basis to explain the reported associations between particulate matter and adverse health effects, and (3) no consensus among the members of the Clean Air Scientific Advisory Committee (CASAC) as to what an appropriate PM indicator, averaging period, or value would be for the revised standard. ^ This project recommends and demonstrates a tool, integrated assessment (IA), to aid the Administrator in making a public health policy decision in the face of ambiguous scientific factors. IA is an interdisciplinary approach to decision making that has been used to deal with complex issues involving many uncertainties, particularly climate change analyses. Two IA approaches are presented; a rough set analysis by which the expertise of CASAC members can be better utilized, and a flag model for incorporating the views of stakeholders into the standard setting process. ^ The rough set analysis can describe minimal and maximal conditions about the current science pertaining to PM and health effects. Similarly, a flag model can evaluate agreement or lack of agreement by various stakeholder groups to the proposed standard in the PM review process. ^ The use of these IA tools will enable the Administrator to (1) complete the NAAQS review in a manner that is in closer compliance with the Clean Air Act, (2) expand the input from CASAC, (3) take into consideration the views of the stakeholders, and (4) retain discretionary decision making authority. ^

Global practice experience: A useful lens for understanding patient and staff perceptions of successful integration of health information technology in primary care

Making healthcare comprehensive and more efficient remains a complex challenge. Health Information Technology (HIT) is recognized as an important component of this transformation but few studies describe HIT adoption and it's effect on the bedside experience by physicians, staff and patients. This study applied descriptive statistics and correlation analysis to data from the Patient-Centered Medical Home National Demonstration Project (NDP) of the American Academy of Family Physicians. Thirty-six clinics were followed for 26 months by clinician/staff questionnaires and patient surveys. This study characterizes those clinics as well as staff and patient perspectives on HIT usefulness, the doctor-patient relationship, electronic medical record (EMR) implementation, and computer connections in the practice throughout the study. The Global Practice Experience factor, a composite score related to key components of primary care, was then correlated to clinician and patient perspectives. This study found wide adoption of HIT among NDP practices. Patient perspectives on HIT helpfulness on the doctor-patient showed a suggestive trend that approached statistical significance (p = 0.172). Clinicians and staff noted successful integration of EMR into clinic workflow and their perception of helpfulness to the doctor-patient relationship show a suggestive increase also approaching statistical significance (p=0.06). GPE was correlated with clinician/staff assessment of a helpful doctor-patient relationship midway through the study (R 0.460, p = 0.021) with the remaining time points nearing statistical significance. GPE was also correlated to both patient perspectives of EMR helpfulness in the doctor-patient relationship (R 0.601, p = 0.001) and computer connections (R 0.618, p = 0.0001) at the start of the study. ^

Genetic integration of a nuclear -encoded mitochondrial gene with cardiac function

Cardiovascular disease (CVD) is the leading cause of death in the United States. One manifestation of CVD known to increase mortality is an enlarged, or hypertrophic heart. Hypertrophic cardiomyocytes adapt to increased contractile demand at the genetic level with a re-emergence of the fetal gene program and a downregulation of fatty acid oxidation genes with concomitant increased reliance on glucose-based metabolism. To understand the transcriptional regulatory pathways that implement hypertrophic directives we analyzed the upstream promoter region of the muscle specific isoform of the nuclear-encoded mitochondrial gene, carnitine palmitoyltransferase-1β (CPT-1β) in cultured rat neonatal cardiac myocytes. This enzyme catalyzes the rate-limiting step of fatty acid entry into β-oxidation and is downregulated in cardiac hypertrophy and failure, making it an attractive model for the study of hypertrophic gene regulation and metabolic adaptations. We demonstrate that the muscle-enriched transcription factors GATA-4 and SRF synergistically activate CPT-1β; moreover, DNA binding to cognate sites and intact protein structure are required. This mechanism coordinates upregulation of energy generating processes with activation of the energy consuming contractile promoter for cardiac α-actin. We hypothesized that fatty acid or glucose responsive transcription factors may also regulate CPT-1β. Oleate weakly stimulates CPT-1β activity; in contrast, the glucose responsive Upstream Stimulatory Factors (USF) dramatically depresses the CPT-1β reporter. USF regulates CPT-1β through a novel physical interaction with the cofactor PGC-1 and abrogation of MEF2A/PGC-1 synergistic stimulation. In this way, USF can inversely regulate metabolic gene programs and may play a role in the shift of metabolic substrate preference seen in hypertrophy. Failing hearts have elevated expression of the nuclear hormone receptor COUP-TF. We report that COUP-TF significantly suppresses reporter transcription independent of DNA binding and specific interactions with GATA-4, Nkx2.5 or USF. In summary, CPT-1β transcriptional regulation integrates mitochondrial gene expression with two essential cardiac functions: contraction and metabolic substrate oxidation. ^